Blood processing systems and methods used to generate plasma typically withdraw whole blood from a patient. The whole blood is then directed to a separator, such as a centrifugal or membrane assembly, for separation of the plasma from the remaining blood components. In most cases, after collecting the plasma the remaining separated constituent components are returned to the patient together with one or more fluids to replace the plasma retained by the system. In the plasma collection procedure, it is generally desired to maintain a patient's fluid balance such that the difference between the amounts of removed fluid and replaced fluid is within a desired range.
There two common separators used in the process of plasma separation—a centrifuge or a plasma filter. When plasma is generated through use of a centrifuge, there are two plasmapheresis methods available: discontinuous flow centrifugation and continuous flow centrifugation. In discontinuous flow centrifugation, a discrete amount of blood is removed (approximately 300 ml) from the patient. Once the blood has been removed, blood plasma is separated through the action of the centrifuge, the non-plasma components are returned to the patient, and the plasma is collected. An advantage of discontinuous flow centrifugation is that only one venous line is required as blood is not removed until the centrifuge has generated the plasma and returned the non-plasma components to the patient. In continuous flow centrifugation, two venous lines are used to allow for concurrent removal of blood and return of non-plasma constituents to the patient. An advantage to this is that it can occur continuously.
The other common plasma separator is a plasma filter. When a plasma filter is used to generate plasma, this plasmapheresis method is generally referred to as plasma filtration. During plasma filtration, two venous lines are used to collect plasma through standard hemodialysis methods.
Hemodialysis is a process which employs a machine that includes a dialyzer with a semipermeable membrane to aide renal patients in the process of urea removal. The membrane serves to divide the dialyzer into two chambers. Blood is pumped through one chamber and a dialysis solution through the second. As the blood flows by the dialysis fluid, impurities, such as urea and creatinine, diffuse through the semipermeable membrane into the dialysis solution. Other purification techniques and processes may additionally be used. One such example is hemodiafiltration, which combines standard dialysis and hemofiltration into one process, whereby convective and diffusive clearance are achieved through the use of substitution fluid.
In the case of plasma filtration, a specialized dialyzer, i.e. a plasma dialyzer, is used instead of a standard dialyzer. The difference between these two types of dialyzers is the pore size of the dialyzer fibers. Typically, a standard dialyzer has fibers with a pore size cut off around 60,000 daltons to minimize the loss of desired blood components such as albumin, whereas a plasma dialyzer has fibers with a pore size greater than 60,000 daltons.
In standard dialysis, fresh dialysate solution, generally composed of reverse osmosis water, salt concentrate, and bicarbonate concentrates enters into one of the two dialysate ports of the dialyzer. The removal of uremic toxins is accomplished by diffusion resultant of the establishment of a concentration gradient between the blood in the inner chamber of the dialyzer and the dialysate in the outside chamber of the dialyzer. After diffusion of uremic toxins from the blood across the semipermeable into the dialysate occurs, the spent dialysate solution exits the second dialysate port of the dialyzer and is returned to the machine to be discarded. Additionally, in some cases the spent dialysate is directed to a re-use cartridge, such as a sorbent cartridge, so that the spent dialysate can be re-incorporated into the fresh dialysate stream after purging the associated uremic toxins.
In plasma filtration, blood enters into a plasma dialyzer with dialyzer fibers with pore size that exceeds that of a standard dialyzer. As a result, albumin, along with the plasma itself is easily capable of traversing the semipermeable membrane of the dialyzer and only larger molecular weight molecules such as red blood cells are prevented from traversing the membrane. Examples of such filters include the Evacure and Evaclio plasma separators from LINC medical, the Monet filter from Fresenius Medical Care, and the PlasmaFlo™ from Apheresis Technologies, Inc.
As a result of the distinction in the use of the dialyzer, the two dialysate ports are not used in an analogous way to dialysis. Instead of fresh dialysate entering one port and spent dialysate exiting the other, a portion of the blood plasma travels across the semipermeable membrane and exits one port of the dialyzer. The second dialyzer port is either not used, or used as a port to monitor pressure. Substitution fluid or saline must be introduced immediately after the plasma dialyzer through use of a fluid pump to replace the plasma that traverses the semipermeable membrane to maintain fluid balance. Additionally, the substitution fluid aides in the flow of the red-blood cells through the plasma dialyzer by reducing the hematocrit in the red-blood cell/plasma solution that exits the blood outlet port of the dialyzer. The intent of this substitution fluid addition is to maintain the hematocrit of the red-blood cell/plasma solution exiting the dialyzer.
It also is generally the case for plasma filtration that a plasma pump is located downstream of the dialyzer port where the plasma exits the dialyzer. The purpose of this pump is to help facilitate the movement of the blood plasma through use of the pump with concurrent monitoring of the pressure in the plasma dialyzer at the second dialysate port. An anticoagulant such as Citrate or Heparin is also generally used for standard dialysis, plasma filtration, and continuous/discontinuous flow centrifugation. If it were desired to collect red blood cells instead of blood plasma, similar limitations may apply.
A limitation of plasma filtration is that the rate of plasma generated at the output of the plasma dialyzer dialysate port can only be a fraction of the input rate of whole blood into the dialyzer. This is because a fraction of the blood plasma will also exit through the blood outlet of the plasma dialyzer along with the red blood cell solution.
Accordingly, it would be desirable to provide a more efficient plasma generation method that may generate plasma at a rate approaching the rate of whole blood entering into the plasma dialyzer. It would also be desirable to provide a plasma generation method that does not require a plasma pump to facilitate the movement of blood plasma or a saline pump to maintain fluid balance, yet may still facilitate the movement of plasma across the semipermeable membrane in an analogous way.
Additionally, it would be desirable to provide a more efficient technique of red blood cell generation that does not require a plasma pump to facilitate the movement of blood plasma or a saline pump to maintain fluid balance.
Further, it would also be desirable to enhance current plasmadiafiltration techniques.